title: Insight into polycation chain length affecting transfection efficiency by O-methyl-free N,N,N-trimethyl chitosans as gene carriers.
abstract: OBJECTIVE
  The structure-function relationship and mechanism of polycations as gene carriers have attracted considerable research interest in recent years. The present study was to investigate the relationship between polycation chain length and transfection efficiency (RCL-TE), and the corresponding mechanism by O-methyl-free N,N,N-trimethyl chitosans (TMCs) as gene carriers.
  
  
  METHODS
  Four TMCs with various chain lengths were synthesized and used to evaluate the RCL-TE. To investigate the details of RCL-TE, a number of factors such as cytotoxicity, cellular uptake efficiency, cellular uptake pathway and intracellular trafficking, were evaluated.
  
  
  RESULTS
  In comparison to short chain length TMCs (S-TMCs), long chain length ones (L-TMCs) mediated higher gene expression. The polyplexes formed by L-TMCs and pDNA showed higher stability. The cellular uptake pathway and intracellular trafficking of these TMC/pDNA polyplexes were different. These above factors are probably the key ones in RCL-TE rather than polycation-DNA binding affinity, polyplex particle size in water, zeta potential, serum, cytotoxicity, and cellular uptake efficiency.
  
  
  CONCLUSIONS
  For rational design of chitosan-based polycations as gene carriers, polycations with relative long chain lengths are more favorable and more attention should be paid to polyplex stability, function of uncomplexed polycation chains, cellular uptake pathway, and intracellular trafficking.
authors.affiliation: State Key Laboratory of Molecular Engineering of Polymer Advanced Materials Laboratory, Department of Macromolecular Science, Fudan University, Shanghai, 200433, People's Republic of China.
authors.forename: Tao
authors.initials: T
authors.lastname: Xu
authors.forename: Suhang
authors.initials: S
authors.lastname: Wang
authors.forename: Zhengzhong
authors.initials: Z
authors.lastname: Shao
mesh_terms: D000818:Animals; D019556:COS Cells; D048271:Chitosan / Q000737:chemistry*; D002522:Chlorocebus aethiops; D018014:Gene Transfer Techniques; D011073:Polyamines / Q000737:chemistry*; D000071228:Polyelectrolytes; D014162:Transfection / Q000379:methods*
chemical_list: D048271:Chitosan; D011073:Polyamines; D000071228:Polyelectrolytes; C118071:N-trimethyl chitosan chloride